相关实验视频

Updated: Jun 4, 2025

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

发现了一种具有RAB11抑制作用的小分子

Camille Lempicki¹, Julian Milosavljevic¹, Christian Laggner²

¹Renal Division, Department of Medicine, Faculty of Medicine, Medical Center, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.

International journal of molecular sciences

|December 17, 2024

概括

研究人员通过计算查和实验验证确定了抑制RAB11 (细胞过程中的关键蛋白质) 的小分子. 这一发现为与RAB11功能障碍相关的疾病提供了潜在的新疗法.

科学领域:

生物化学生化学
细胞生物学细胞生物学
药物发现药物发现药物发现

背景情况:

一种RabGTPase的RAB11对于细胞功能至关重要,例如内细胞循环,外细胞和自.
RAB11的失调与各种疾病有关,包括癌症和神经退行性疾病.
缺乏特定的小分子抑制剂阻碍了针对RAB11相关疾病的研究和治疗开发.

研究的目的:

开发一种方法来识别RAB11蛋白的小分子抑制剂.
通过体外和体外模型验证潜在的抑制剂.

主要方法:

利用基于深度学习的计算选来识别潜在的RAB11抑制剂.
采用一个体外平台测量GFP外细胞形成,以验证化合物活性.
评估了化合物对自和Rab11囊泡局部化的影响.
在*Drosophila*模型中验证的发现,评估毒性和RAB11依赖功能.

主要成果:

在基选中确定了94种候选化合物,其中9种在RAB11活性方面在体外得到了验证.
证实了三种强大的化合物可以调节自.
两种化合物改变了Rab11囊泡的位置,但没有影响Rab5或Rab7.
*Drosophila*研究表明,一种候选化合物具有低毒性,并抑制了依赖RAB11的细胞功能.

结论:

一种结合计算和实验方法成功地确定了调节RAB11功能的小分子.
这些已识别的化合物代表了开发RAB11相关疾病治疗方法的有希望的线索.

关键词:

果虫脏细胞 (Drosophila nephrocyte) 是一种细胞.拉伯11 拉伯11 拉伯11 拉伯11 拉伯11 拉伯11 发现药物的发现.细胞内的形成细胞内的形成高通量选的高通量选机器学习是机器学习.虚拟选是虚拟的选.

更多相关视频

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

Inducible and Reversible Dominant-negative DN Protein Inhibition

Inducible and Reversible Dominant-negative DN Protein Inhibition

Published on: January 7, 2019

相关概念视频

Rab Proteins

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...

Rab Cascades

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.

Small GTPases - Ras and Rho

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:

Feedback Inhibition

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!

Recycling Endosomes and Transcytosis

Recycling Endosomes and Transcytosis

The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...

Experimental RNAi

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...